IE67133B1 - Benzimidazole derivatives their preparation and use - Google Patents

Benzimidazole derivatives their preparation and use

Info

Publication number: IE67133B1
Authority: IE; Ireland
Prior art keywords: chloro; hydrogen; compound; hydroxyphenyl; dihydro
Prior art date: 1990-09-24

Application number

IE319791A

Other languages

English (en)

Other versions

IE913197A1 (en

Inventor

Soeren-Peter Olesen

Frank Waetjen

Original Assignee

Neurosearch As

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1990-09-24

Filing date

1991-09-11

Publication date

1996-03-06

1991-09-11 Application filed by Neurosearch As filed Critical Neurosearch As

1992-02-25 Publication of IE913197A1 publication Critical patent/IE913197A1/en

1996-03-06 Publication of IE67133B1 publication Critical patent/IE67133B1/en

Links

229940058303 antinematodal benzimidazole derivative Drugs 0.000 title description 3
238000002360 preparation method Methods 0.000 title description 2
125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 88
239000001257 hydrogen Substances 0.000 claims abstract description 24
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 12
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 10
229910052736 halogen Inorganic materials 0.000 claims abstract description 9
150000002367 halogens Chemical class 0.000 claims abstract description 9
150000002431 hydrogen Chemical class 0.000 claims abstract description 9
125000003118 aryl group Chemical group 0.000 claims abstract description 6
238000000034 method Methods 0.000 claims abstract description 6
229920006395 saturated elastomer Polymers 0.000 claims abstract description 6
102000004257 Potassium Channel Human genes 0.000 claims abstract description 5
108020001213 potassium channel Proteins 0.000 claims abstract description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 3
229910052717 sulfur Inorganic materials 0.000 claims abstract 3
239000003814 drug Substances 0.000 claims description 8
206010020772 Hypertension Diseases 0.000 claims description 5
208000006673 asthma Diseases 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
206010010904 Convulsion Diseases 0.000 claims description 4
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 4
230000036461 convulsion Effects 0.000 claims description 4
208000028867 ischemia Diseases 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
241001465754 Metazoa Species 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
125000002837 carbocyclic group Chemical group 0.000 claims description 2
RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 3
125000000217 alkyl group Chemical group 0.000 claims 1
241000124008 Mammalia Species 0.000 abstract description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 5
201000010099 disease Diseases 0.000 abstract description 3
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 3
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 abstract 2
229910052760 oxygen Inorganic materials 0.000 abstract 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
239000000203 mixture Substances 0.000 description 29
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
239000013078 crystal Substances 0.000 description 26
239000000543 intermediate Substances 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 22
239000000243 solution Substances 0.000 description 21
239000000047 product Substances 0.000 description 20
108091006146 Channels Proteins 0.000 description 19
239000003054 catalyst Substances 0.000 description 19
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
-1 M-(2-benzimidazolyl)-4-piperidinamines Chemical class 0.000 description 17
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
238000000746 purification Methods 0.000 description 15
239000007868 Raney catalyst Substances 0.000 description 14
229910000564 Raney nickel Inorganic materials 0.000 description 14
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 13
239000003921 oil Substances 0.000 description 13
235000019198 oils Nutrition 0.000 description 13
239000011541 reaction mixture Substances 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
238000001914 filtration Methods 0.000 description 10
FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
229940039407 aniline Drugs 0.000 description 9
PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-UHFFFAOYSA-N 0.000 description 8
CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
210000004027 cell Anatomy 0.000 description 8
239000012043 crude product Substances 0.000 description 8
MYONAGGJKCJOBT-UHFFFAOYSA-N benzimidazol-2-one Chemical class C1=CC=CC2=NC(=O)N=C21 MYONAGGJKCJOBT-UHFFFAOYSA-N 0.000 description 7
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
229960004132 diethyl ether Drugs 0.000 description 5
150000002500 ions Chemical class 0.000 description 5
239000004323 potassium nitrate Substances 0.000 description 5
235000010333 potassium nitrate Nutrition 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 description 4
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
229960000583 acetic acid Drugs 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
208000035475 disorder Diseases 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000003480 eluent Substances 0.000 description 4
230000002102 hyperpolarization Effects 0.000 description 4
239000012528 membrane Substances 0.000 description 4
239000012071 phase Substances 0.000 description 4
239000012312 sodium hydride Substances 0.000 description 4
229910000104 sodium hydride Inorganic materials 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
WBSMIPLNPSCJFS-UHFFFAOYSA-N 5-chloro-2-methoxyaniline Chemical compound COC1=CC=C(Cl)C=C1N WBSMIPLNPSCJFS-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
TVZCRIROJQEVOT-CABCVRRESA-N Cromakalim Chemical compound N1([C@@H]2C3=CC(=CC=C3OC([C@H]2O)(C)C)C#N)CCCC1=O TVZCRIROJQEVOT-CABCVRRESA-N 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
150000001556 benzimidazoles Chemical class 0.000 description 3
TZFWDZFKRBELIQ-UHFFFAOYSA-N chlorzoxazone Chemical compound ClC1=CC=C2OC(O)=NC2=C1 TZFWDZFKRBELIQ-UHFFFAOYSA-N 0.000 description 3
238000001816 cooling Methods 0.000 description 3
239000012362 glacial acetic acid Substances 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000003208 petroleum Substances 0.000 description 3
238000010992 reflux Methods 0.000 description 3
239000011734 sodium Substances 0.000 description 3
TZGFQIXRVUHDLE-UHFFFAOYSA-N 1-chloro-2-nitro-4-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(C(F)(F)F)=CC=C1Cl TZGFQIXRVUHDLE-UHFFFAOYSA-N 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 2
DTYBRSLINXBXMP-UHFFFAOYSA-N 2-methoxy-5-phenylaniline Chemical compound C1=C(N)C(OC)=CC=C1C1=CC=CC=C1 DTYBRSLINXBXMP-UHFFFAOYSA-N 0.000 description 2
BUNCHTGWWPOJFZ-UHFFFAOYSA-N 2-n-(3,5-dichloro-2-methoxyphenyl)benzene-1,2-diamine Chemical compound COC1=C(Cl)C=C(Cl)C=C1NC1=CC=CC=C1N BUNCHTGWWPOJFZ-UHFFFAOYSA-N 0.000 description 2
CHOYJIAPCQNFES-UHFFFAOYSA-N 2-n-(5-chloro-2-methoxyphenyl)benzene-1,2-diamine Chemical compound COC1=CC=C(Cl)C=C1NC1=CC=CC=C1N CHOYJIAPCQNFES-UHFFFAOYSA-N 0.000 description 2
HLEFTZPTWXTBQZ-UHFFFAOYSA-N 3-(2-nitrophenyl)-1,3-benzoxazol-2-one Chemical compound [O-][N+](=O)C1=CC=CC=C1N1C(=O)OC2=CC=CC=C21 HLEFTZPTWXTBQZ-UHFFFAOYSA-N 0.000 description 2
CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 2
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
239000002253 acid Substances 0.000 description 2
230000003213 activating effect Effects 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
230000001088 anti-asthma Effects 0.000 description 2
230000002082 anti-convulsion Effects 0.000 description 2
239000001110 calcium chloride Substances 0.000 description 2
235000011148 calcium chloride Nutrition 0.000 description 2
229910001628 calcium chloride Inorganic materials 0.000 description 2
239000002775 capsule Substances 0.000 description 2
229950004210 cromakalim Drugs 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000005457 ice water Substances 0.000 description 2
210000002569 neuron Anatomy 0.000 description 2
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Substances [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical compound COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
108010083133 potassium channel protein I(sk) Proteins 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
239000002002 slurry Substances 0.000 description 2
210000002460 smooth muscle Anatomy 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000002904 solvent Substances 0.000 description 2
210000005090 tracheal smooth muscle Anatomy 0.000 description 2
210000004509 vascular smooth muscle cell Anatomy 0.000 description 2
YBDBYPQFIMSFJW-UHFFFAOYSA-N (4-chloro-3-nitrophenyl)-phenylmethanone Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC(C(=O)C=2C=CC=CC=2)=C1 YBDBYPQFIMSFJW-UHFFFAOYSA-N 0.000 description 1
FXOCDIKCKFOUDE-UHFFFAOYSA-N 1,2-dichloro-4-fluoro-5-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(Cl)=C(Cl)C=C1F FXOCDIKCKFOUDE-UHFFFAOYSA-N 0.000 description 1
AXLDWMVASPWDQF-UHFFFAOYSA-N 1,3-bis(2-methoxyphenyl)urea Chemical compound COC1=CC=CC=C1NC(=O)NC1=CC=CC=C1OC AXLDWMVASPWDQF-UHFFFAOYSA-N 0.000 description 1
SILNNFMWIMZVEQ-UHFFFAOYSA-N 1,3-dihydrobenzimidazol-2-one Chemical class C1=CC=C2NC(O)=NC2=C1 SILNNFMWIMZVEQ-UHFFFAOYSA-N 0.000 description 1
XEKUGBDRFVFLEA-UHFFFAOYSA-N 1-(5-chloro-2-hydroxyphenyl)-3-methyl-5-(trifluoromethyl)benzimidazol-2-one Chemical compound O=C1N(C)C2=CC(C(F)(F)F)=CC=C2N1C1=CC(Cl)=CC=C1O XEKUGBDRFVFLEA-UHFFFAOYSA-N 0.000 description 1
CISRHMUOOJKICE-UHFFFAOYSA-N 1-(fluoromethyl)-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1CF CISRHMUOOJKICE-UHFFFAOYSA-N 0.000 description 1
NJKHAMDETWXUAY-UHFFFAOYSA-N 1-[2-nitro-4-(trifluoromethyl)anilino]naphthalen-2-ol Chemical compound OC1=CC=C2C=CC=CC2=C1NC1=CC=C(C(F)(F)F)C=C1[N+]([O-])=O NJKHAMDETWXUAY-UHFFFAOYSA-N 0.000 description 1
FHMMQQXRSYSWCM-UHFFFAOYSA-N 1-aminonaphthalen-2-ol Chemical compound C1=CC=C2C(N)=C(O)C=CC2=C1 FHMMQQXRSYSWCM-UHFFFAOYSA-N 0.000 description 1
HISHUMDTGXICEZ-UHFFFAOYSA-N 1-chloro-4-methoxy-2-nitrobenzene Chemical compound COC1=CC=C(Cl)C([N+]([O-])=O)=C1 HISHUMDTGXICEZ-UHFFFAOYSA-N 0.000 description 1
IVVNZDGDKPTYHK-JTQLQIEISA-N 1-cyano-2-[(2s)-3,3-dimethylbutan-2-yl]-3-pyridin-4-ylguanidine Chemical compound CC(C)(C)[C@H](C)N=C(NC#N)NC1=CC=NC=C1 IVVNZDGDKPTYHK-JTQLQIEISA-N 0.000 description 1
HLDFCCHSOZWKAA-UHFFFAOYSA-N 1-fluoro-2-nitro-4-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(C(F)(F)F)=CC=C1F HLDFCCHSOZWKAA-UHFFFAOYSA-N 0.000 description 1
OLTNHAVUPCKTQR-UHFFFAOYSA-N 1-n-(5-chloro-2-methoxyphenyl)-4-(trifluoromethyl)benzene-1,2-diamine Chemical compound COC1=CC=C(Cl)C=C1NC1=CC=C(C(F)(F)F)C=C1N OLTNHAVUPCKTQR-UHFFFAOYSA-N 0.000 description 1
NMGHEOHOYKBWEM-UHFFFAOYSA-N 2,4-dichloro-6-methoxyaniline Chemical compound COC1=CC(Cl)=CC(Cl)=C1N NMGHEOHOYKBWEM-UHFFFAOYSA-N 0.000 description 1
KYAGPEYJRITJLT-UHFFFAOYSA-N 2,4-dichloro-n-(5-chloro-2-methoxyphenyl)-6-nitroaniline Chemical compound COC1=CC=C(Cl)C=C1NC1=C(Cl)C=C(Cl)C=C1[N+]([O-])=O KYAGPEYJRITJLT-UHFFFAOYSA-N 0.000 description 1
RJXOVESYJFXCGI-UHFFFAOYSA-N 2,4-difluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1F RJXOVESYJFXCGI-UHFFFAOYSA-N 0.000 description 1
MDFOQYKZQPTLON-UHFFFAOYSA-N 2-(2-amino-4,5-dichloroanilino)phenol Chemical compound NC1=CC(Cl)=C(Cl)C=C1NC1=CC=CC=C1O MDFOQYKZQPTLON-UHFFFAOYSA-N 0.000 description 1
XGKHCLSGQDOGPD-UHFFFAOYSA-N 2-(2-aminoanilino)benzenethiol Chemical compound NC1=CC=CC=C1NC1=CC=CC=C1S XGKHCLSGQDOGPD-UHFFFAOYSA-N 0.000 description 1
LYEZXOMDMACXMT-UHFFFAOYSA-N 2-(2-aminoanilino)phenol Chemical compound NC1=CC=CC=C1NC1=CC=CC=C1O LYEZXOMDMACXMT-UHFFFAOYSA-N 0.000 description 1
XRXKXMZZICZXGN-UHFFFAOYSA-N 2-(2-nitroanilino)phenol Chemical compound OC1=CC=CC=C1NC1=CC=CC=C1[N+]([O-])=O XRXKXMZZICZXGN-UHFFFAOYSA-N 0.000 description 1
KFCHOCXCZVZSHQ-UHFFFAOYSA-N 2-methoxy-n-(2-nitrophenyl)-5-phenylaniline Chemical compound COC1=CC=C(C=2C=CC=CC=2)C=C1NC1=CC=CC=C1[N+]([O-])=O KFCHOCXCZVZSHQ-UHFFFAOYSA-N 0.000 description 1
SMXSFWBFEVJOMM-UHFFFAOYSA-N 2-methoxy-n-[2-nitro-4-(trifluoromethyl)phenyl]-4-phenylaniline Chemical compound COC1=CC(C=2C=CC=CC=2)=CC=C1NC1=CC=C(C(F)(F)F)C=C1[N+]([O-])=O SMXSFWBFEVJOMM-UHFFFAOYSA-N 0.000 description 1
RRMVBUOCCIVITB-UHFFFAOYSA-N 2-n-(2-methoxyphenyl)benzene-1,2-diamine Chemical compound COC1=CC=CC=C1NC1=CC=CC=C1N RRMVBUOCCIVITB-UHFFFAOYSA-N 0.000 description 1
DPJCXCZTLWNFOH-UHFFFAOYSA-N 2-nitroaniline Chemical compound NC1=CC=CC=C1[N+]([O-])=O DPJCXCZTLWNFOH-UHFFFAOYSA-N 0.000 description 1
SDYWXFYBZPNOFX-UHFFFAOYSA-N 3,4-dichloroaniline Chemical compound NC1=CC=C(Cl)C(Cl)=C1 SDYWXFYBZPNOFX-UHFFFAOYSA-N 0.000 description 1
LCEPTDOGPNFBKZ-UHFFFAOYSA-N 3,5-dichloro-2-methoxy-N-phenylaniline Chemical compound ClC=1C(=C(C=C(C=1)Cl)NC1=CC=CC=C1)OC LCEPTDOGPNFBKZ-UHFFFAOYSA-N 0.000 description 1
PGBYLHRVUUPEQL-UHFFFAOYSA-N 3,5-dichloro-2-methoxy-n-(2-nitrophenyl)aniline Chemical compound COC1=C(Cl)C=C(Cl)C=C1NC1=CC=CC=C1[N+]([O-])=O PGBYLHRVUUPEQL-UHFFFAOYSA-N 0.000 description 1
PBNWKXJMRPRROE-UHFFFAOYSA-N 3,5-dichloro-2-n-(5-chloro-2-methoxyphenyl)benzene-1,2-diamine Chemical compound COC1=CC=C(Cl)C=C1NC1=C(N)C=C(Cl)C=C1Cl PBNWKXJMRPRROE-UHFFFAOYSA-N 0.000 description 1
PIBZOHJUHDVUDG-UHFFFAOYSA-N 3-(2-hydroxyphenyl)-6-(trifluoromethyl)-1h-benzimidazol-2-one Chemical compound OC1=CC=CC=C1N1C(=O)NC2=CC(C(F)(F)F)=CC=C21 PIBZOHJUHDVUDG-UHFFFAOYSA-N 0.000 description 1
BSPOIJPFILZYTK-UHFFFAOYSA-N 3-(2-nitrophenyl)-1,3-benzothiazol-2-one Chemical compound [O-][N+](=O)C1=CC=CC=C1N1C(=O)SC2=CC=CC=C21 BSPOIJPFILZYTK-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/12—Radicals substituted by oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/26—Oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/28—Sulfur atoms

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Pulmonology (AREA)
Vascular Medicine (AREA)
Pain & Pain Management (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Polyesters Or Polycarbonates (AREA)
Graft Or Block Polymers (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

IE319791A 1990-09-24 1991-09-11 Benzimidazole derivatives their preparation and use IE67133B1 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US58690090A	1990-09-24	1990-09-24

Publications (2)

Publication Number	Publication Date
IE913197A1 IE913197A1 (en)	1992-02-25
IE67133B1 true IE67133B1 (en)	1996-03-06

Family

ID=24347548

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IE319791A IE67133B1 (en)	1990-09-24	1991-09-11	Benzimidazole derivatives their preparation and use

Country Status (15)

Country	Link
EP (1)	EP0477819B1 (de)
JP (1)	JP3203017B2 (de)
KR (1)	KR100195770B1 (de)
AT (1)	ATE119887T1 (de)
AU (1)	AU635440B2 (de)
CA (1)	CA2052041C (de)
DE (1)	DE69108156T2 (de)
DK (1)	DK0477819T3 (de)
ES (1)	ES2072504T3 (de)
FI (1)	FI103408B (de)
IE (1)	IE67133B1 (de)
NO (1)	NO180795C (de)
NZ (1)	NZ239540A (de)
PT (1)	PT99032B (de)
ZA (1)	ZA916805B (de)

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* Cited by examiner, † Cited by third party
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ATE163290T1 (de) *	1991-06-24	1998-03-15	Neurosearch As	Imidazol-verbindungen, verfahren zu ihrer herstellung und ihre anwendung
US5158969A (en) *	1991-08-21	1992-10-27	Neurosearch A/S	Indole derivatives as potassium channel blockers
US5232899A (en) *	1992-06-08	1993-08-03	Imperial Chemical Industries Plc	Benzoxazolinones and their use as herbicides
AU5433594A (en) *	1992-11-19	1994-06-08	Dainippon Pharmaceutical Co. Ltd.	3,4-dihydro-1-(2-hydroxyphenyl)-2(1h)-quinoxalinone derivative and related compound
DK154092D0 (da) *	1992-12-23	1992-12-23	Neurosearch As	Imidazolforbindelser, deres fremstilling og anvendelse
DK28893D0 (da) *	1993-03-15	1993-03-15	Neurosearch As	Benzimidazole derivater, deres fremstilling og anvendelse
DK41193D0 (da) *	1993-04-07	1993-04-07	Neurosearch As	Ionkanalaabnere
US5637470A (en) *	1994-05-13	1997-06-10	Merck & Co., Inc.	Screening array using cells expressing recombinant α and β subunits of the mammalian large-conductance (maxi-K) potassium channel
FR2722190B1 (fr) *	1994-07-05	1996-10-04	Sanofi Sa	Derives de 1-benzyl-1,3-dihydro-2h-benzimidazol-2-one, leur preparation, les compositions pharmaceutique en contenant
US5565483A (en) *	1995-06-07	1996-10-15	Bristol-Myers Squibb Company	3-substituted oxindole derivatives as potassium channel modulators
TW504504B (en) *	1996-11-26	2002-10-01	Bristol Myers Squibb Co	4-aryl-3-hydroxyquinolin-2-one derivatives as ion channel modulators
US5893085A (en) *	1997-06-10	1999-04-06	Phillips; Ronald W.	Dynamic fuzzy logic process for identifying objects in three-dimensional data
AU742452B2 (en) *	1997-08-28	2002-01-03	Bristol-Myers Squibb Company	4-aryl-3-aminoquinoline-2-one derivatives as potassium channel modulators
PT1133474E (pt)	1998-12-04	2007-04-30	Bristol Myers Squibb Co	Derivados da 4-arilquinolin-2-ona substituidos em 3 posições utilizados como moduladores do canal de potássio.
CA2349616A1 (en)	1998-12-04	2000-06-15	Neurosearch A/S	New benzimidazolone-, benzoxazolone-, or benzothiazolone derivatives as ion channel modulating agents
JP2005533814A (ja) *	2002-06-26	2005-11-10	ポセイドン・ファーマスーティカルス・アクティーゼルスカブ	新規ベンズイミダゾール−２−オン誘導体及びその使用方法
WO2004064835A1 (en) *	2003-01-17	2004-08-05	Neurosearch A/S	Use of ion channel modulating agents for treating pain
ES2222831B2 (es) *	2003-07-30	2006-02-16	Laboratorios Del Dr. Esteve, S.A.	Combinacion de principio activo que comprende un compuesto 2,5-dihidroxibencenosulfonico y un modulador de los canales de k+.
PE20060572A1 (es) *	2004-07-27	2006-06-27	Novartis Ag	Compuestos de benzoimidazolona como inhibidores de hsp90
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1991
- 1991-08-26 NZ NZ239540A patent/NZ239540A/en not_active IP Right Cessation
- 1991-08-28 AU AU82767/91A patent/AU635440B2/en not_active Ceased
- 1991-08-28 ZA ZA916805A patent/ZA916805B/xx unknown
- 1991-09-11 IE IE319791A patent/IE67133B1/en not_active IP Right Cessation
- 1991-09-11 FI FI914275A patent/FI103408B/fi not_active IP Right Cessation
- 1991-09-20 KR KR1019910016522A patent/KR100195770B1/ko not_active Expired - Fee Related
- 1991-09-20 JP JP24194691A patent/JP3203017B2/ja not_active Expired - Fee Related
- 1991-09-23 EP EP91116148A patent/EP0477819B1/de not_active Expired - Lifetime
- 1991-09-23 CA CA002052041A patent/CA2052041C/en not_active Expired - Fee Related
- 1991-09-23 DK DK91116148.7T patent/DK0477819T3/da active
- 1991-09-23 DE DE69108156T patent/DE69108156T2/de not_active Expired - Fee Related
- 1991-09-23 NO NO913728A patent/NO180795C/no unknown
- 1991-09-23 AT AT91116148T patent/ATE119887T1/de not_active IP Right Cessation
- 1991-09-23 ES ES91116148T patent/ES2072504T3/es not_active Expired - Lifetime
- 1991-09-24 PT PT99032A patent/PT99032B/pt not_active IP Right Cessation

Also Published As

Publication number	Publication date
NO913728L (no)	1992-03-25
NO180795B (no)	1997-03-17
JP3203017B2 (ja)	2001-08-27
FI103408B1 (fi)	1999-06-30
DE69108156T2 (de)	1995-07-06
ES2072504T3 (es)	1995-07-16
KR100195770B1 (ko)	1999-06-15
JPH04305568A (ja)	1992-10-28
KR920006327A (ko)	1992-04-27
NO180795C (no)	1997-06-25
ZA916805B (en)	1992-05-27
AU8276791A (en)	1992-03-26
EP0477819A3 (en)	1992-05-20
CA2052041A1 (en)	1992-03-25
CA2052041C (en)	2002-08-20
FI103408B (fi)	1999-06-30
DE69108156D1 (de)	1995-04-20
FI914275A0 (fi)	1991-09-11
ATE119887T1 (de)	1995-04-15
FI914275L (fi)	1992-03-25
IE913197A1 (en)	1992-02-25
EP0477819A2 (de)	1992-04-01
PT99032A (pt)	1993-11-30
DK0477819T3 (da)	1995-07-17
NZ239540A (en)	1993-11-25
NO913728D0 (no)	1991-09-23
PT99032B (pt)	1999-02-26
AU635440B2 (en)	1993-03-18
EP0477819B1 (de)	1995-03-15

Legal Events

Date	Code	Title	Description
2009-06-24	MM4A	Patent lapsed

Publication	Publication Date	Title
IE67133B1 (en)	1996-03-06	Benzimidazole derivatives their preparation and use
US5200422A (en)	1993-04-06	Benzimidazole derivatives, their preparation and use
CA2381819C (en)	2007-03-13	New benzimidazolone derivatives having mixed serotonine and dopamine receptors affinity
US5166170A (en)	1992-11-24	2-(aminoaryl) indoles and indolines as topical antiinflammatory agents for the treatment of skin disorders
Le Bihan et al.	1999	Design and Synthesis of Imidazoline Derivatives Active on Glucose Homeostasis in a Rat Model of Type II Diabetes. 2. Syntheses and Biological Activities of 1, 4-Dialkyl-, 1, 4-Dibenzyl, and 1-Benzyl-4-alkyl-2-(4 ‘, 5 ‘-dihydro-1 ‘H-imidazol-2 ‘-yl) piperazines and Isosteric Analogues of Imidazoline
EP0260817A1 (de)	1988-03-23	Chinazolindione und Pyridopyrimidindione
CA2497827A1 (en)	2004-03-18	(1h-benzoimidazol-2-yl)-(piperazinyl)-methanone derivatives and related compounds as histamine h4-receptor antagonists for the treatment of inflammatory and allergic disorders
FI60010C (fi)	1981-11-10	Foerfarande foer framstaellning av nya terapeutiskt anvaendbara 4-(2-imidazolin-2-ylamino)-2,1,3-bensotiadiazoler
CA1163266A (en)	1984-03-06	Benzodiazepine derivatives
FI63228C (fi)	1983-05-10	Foerfarande foer framstaellning av 1-bensazolyl-4-substituerade piperidiner anvaendbara saosom neuroleptiska medel
US5214059A (en)	1993-05-25	2-(aminoaryl) indoles and indolines as topical antiinflammatory agents for the treatment of skin disorders
EP0204215A1 (de)	1986-12-10	2-[(1H-Benzimidazol-2-ylsulfonyl)methyl]-benzenamine
US3644382A (en)	1972-02-22	Benzimidazole derivatives of benzoic acid and its esters and amides
CA1059135A (en)	1979-07-24	Anthelmintically active 2-carbalkoxyamino-5 (6)-phenyl sulfonyloxy benzimidazoles and process for their manufacture
HUP0402585A2 (hu)	2005-03-29	Új benzotiazin- benzotiadiazin-származékok, előállításuk, alkalmazásuk és az ezeket tartalmazó gyógyászati készítmények
US3757008A (en)	1973-09-04	Sses for preparing same 1 - (carboxyl-heteroalkyl) - 1,4-benzodiazepine derivatives and proce
IE59937B1 (en)	1994-05-04	Quinazolinediones and pyridopyrimidinediones
US4001408A (en)	1977-01-04	Substituted heterocyclic compounds, processes and composition including those
US6632813B1 (en)	2003-10-14	6-subtituted-7-heteroquinoxalinecarboxylic acid derivatives and addition salts thereof and processes for the preparation of both
US3405123A (en)	1968-10-08	Process for preparing 1, 4-benzodiazepin-2-ones
US3886214A (en)	1975-05-27	Benzodiazepin-2-ones and processes for the preparation thereof
Slavica et al.	1994	Synthesis and biological activities of a new set of irreversibly acting 2-(4'-isothiocyanatobenzyl) imidazoline analogs in rat thoracic aorta
JYOTSNA et al.	1980	SYNTHESIS AND PHARMACOLOGICAL SCREENlNG OF 2’-(6-SULPHONYL-6H-7-METHYL-5-OXO-4H-2, 3-DIHYDRO-1, 4-DIAZEPINO)-2, 5-DIMETHYL-6, 7-BENZOMORPHAN
US3504015A (en)	1970-03-31	N-(2-aroylphenyl)glycine derivatives
US3462418A (en)	1969-08-19	Preparation of 1,4-benzodiazepin-2-one-4-oxide from 2-lower alkoxy-1,4-benzodiazepine-4-oxide